HHS advisors urge full speed on H1N1 vaccine production

Jul 17, 2009 (CIDRAP News)  An expert panel that advises the Department of Health and Human Services (HHS) today supported the idea of moving quickly on pandemic H1N1 vaccine production with a goal of having "tens of millions of doses" available in September instead of October.

Discussing vaccine issues during a public teleconference today, the National Biodefense Science Board (NBSB) favored the idea of asking vaccine makers to start the final production steps for their H1N1 vaccines on Aug 15before the first data from safety and immunogenicity trials will be available.

Last week, HHS Secretary Kathleen Sebelius said it was expected that the first H1N1 doses would be ready for distribution in mid-October. HHS has yet not made a formal decision to go ahead with a vaccination campaign, but Sebelius said the step was likely.

Dr. Robin Robinson, director of HHS's Biomedical Advanced Research and Development Authority (BARDA), told the NBSB that HHS should have some data on the immunogenicity of single-dose H1N1 vaccination in September. If filling and finishingthe final production stepsstart on Sep 15, the first doses will become available about Oct 15, he said.

To make vaccine available in mid-September, filling and finishing would have to start Aug 15, Robinson said. "Certainly the department, including FDA, is seriously considering how this can be done," he said.

Board member Patrick J. Scannon, MD, PhD, said, "There was a considerable sense of urgency that came out of the June meeting because of the possibility that a new wave of H1N1 could come back to us by September. I think that's what's driving this line of questions." He was referring to a June meeting of the board's Pandemic Influenza Working Group, whose report from that meeting was discussed at today's conference.

Robinson said that about 60 million to 80 million doses could be made available starting in September if the decision were made to go ahead with final production steps Aug 15. He said Aug 15 is a "reasonable date" when vaccine makers could start those steps, as they are currently still producing their seasonal flu vaccines.

At this point no one knows if 15 micrograms (mcg) of vaccine antigen, the standard amount used for each flu subtype in seasonal vaccines, will be enough to generate a protective immune response with H1N1 vaccines.

"The FDA is considering if the vaccine could be at the standard dose based on the many years" of using 15 mcg, said Robinson.

Board member Andrew T. Pavia, MD, suggested that the vaccine could be bottled at a concentration of 15 mcg of antigen per 0.5 milliliter (mL) of solution. If trial data later showed a need for a greater dose, it could be doubled by administering 1 mL instead of 0.5 mL, he said.

Pavia said his sense was that the risk in moving ahead "is relatively small compared with the upside of committing at least a portion of the 60 million doses to fill and finish."

Board member John Grabenstein, RPh, PhD, counseled against picking a specific number of doses to produce by September, since the number of people targeted for early vaccination is not yet known. "Our role is to decide whether we want some product by mid-September," he said.

After further discussion, the group agreed to recommend that HHS "set a goal of having several tens of millions of doses available by Sep 15." The vaccine would not contain an adjuvant.

In briefing the board early in today's session, Robinson said HHS has contracted for 193 million doses of vaccine so far, assuming 15 mcg per dose. After 2.5 weeks of production, manufacturers have made 18 million doses worth of bulk vaccine, he said.

HHS has ordered 119 million doses of two different adjuvants, MF59 and ASO3, he reported.

Commenting on reports of low yields of vaccines, which are grown in eggs, Robinson said yields are actually right in line with what HHS had expected from experience with H5N1 vaccines: about 1.4 doses per egg. However, he said the H1N1 vaccine virus apparently contains less hemagglutinin (the antigen) than seasonal strains and is a little harder to purify.

The story is the opposite with the live attenuated H1N1 vaccine being made by MedImmune, Robinson reported. Instead of low yields, the company is getting surprisingly high yields.

"They've already actually made a super virus seed that's actually producing 2 logs titer higher than you'd normally see," he said. "That means there's going to be more bulk product available than we can actually fill."

He said HHS will look for other vendors to help package the extra product, adding, "We may be able to have more live attenuated vaccine than anticipated earlier, so that's good news."

In other comments, Robinson said:

HHS wants to increase the proportion of zanamivir (Relenza) in the national stockpile relative to oseltamivir (Tamiflu), in light of a few recent instances of H1N1 resistance to the latter. The current split is 80% oseltamivir and 20% zanamivir; the agency would like to move to 50-50, but that will take time.

HHS is considering issuing an emergency use authorization for peramivir, an antiviral drug that is in phase 3 clinical trials but not yet licensed. "It's under consideration whether we should have some of that drug available for individuals in desperate need," he said.